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Home / Equine Research Bank / BMC Genomics / Differential gene expression analysis reveals pathways impor...
BMC genomics2020; 21(1); 843; doi: 10.1186/s12864-020-07228-z

Differential gene expression analysis reveals pathways important in early post-traumatic osteoarthritis in an equine model.

Abstract: Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression changes in early disease. In this study, we quantified gene expression changes in the synovium of osteoarthritis-affected joints using an equine metacarpophalangeal joint (MCPJ) chip model of early PTOA. Synovial samples were collected arthroscopically from the MCPJ of 11 adult horses before (preOA) and after (OA) surgical induction of osteoarthritis and from sham-operated joints. After sequencing synovial RNA, Salmon was used to quasi-map reads and quantify transcript abundances. Differential expression analysis with the limma-trend method used a fold-change cutoff of log2(1.1). Functional annotation was performed with PANTHER at FDR < 0.05. Pathway and network analyses were performed in Reactome and STRING, respectively. Results: RNA was sequenced from 28 samples (6 preOA, 11 OA, 11 sham). "Sham" and "preOA" were not different and were grouped. Three hundred ninety-seven genes were upregulated and 365 downregulated in OA synovium compared to unaffected. Gene ontology (GO) terms related to extracellular matrix (ECM) organization, angiogenesis, and cell signaling were overrepresented. There were 17 enriched pathways, involved in ECM turnover, protein metabolism, and growth factor signaling. Network analysis revealed clusters of differentially expressed genes involved in ECM organization, endothelial regulation, and cellular metabolism. Conclusions: Enriched pathways and overrepresented GO terms reflected a state of high metabolic activity and tissue turnover in OA-affected tissue, suggesting that the synovium may retain the capacity to support healing and homeostasis in early disease. Limitations of this study include small sample size and capture of one point post-injury. Differentially expressed genes within key pathways may represent potential diagnostic markers or therapeutic targets for PTOA. Mechanistic validation of these findings is an important next step.
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Publication Date: 2020-11-30 PubMed ID: 33256611PubMed Central: PMC7708211DOI: 10.1186/s12864-020-07228-zGoogle Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research attempts to understand the early stages of post-traumatic osteoarthritis (PTOA) in horses by examining the changes in gene expression in the synovium of affected joints. By doing so, the researchers hope to identify potential diagnostic markers and therapeutic targets for this illness.

Methodology

  • To study the genetic changes related to early-stage PTOA, the researchers used the metacarpophalangeal joint (MCPJ) chip model in 11 adult horses.
  • They collected synovial samples from these horses both before and after the surgical induction of osteoarthritis, as well as from sham-operated joints.
  • Next, RNA was extracted and sequenced from these samples.
  • The sequenced RNA samples were then quasi-mapped and had their transcript abundances quantified using a software package called Salmon.
  • Differential expression analysis was conducted to identify changes in gene expression.
  • Another tool, PANTHER, was used for functional annotation.
  • Lastly, the researchers categorized identified genes into pathways and performed network analyses using Reactome and STRING.

Results

  • From a total of 28 samples, the researchers found 397 genes upregulated and 365 downregulated in the osteoarthritis-affected synovium in comparison to unaffected ones.
  • The Gene Ontology (GO) terms related to extracellular matrix organization, angiogenesis, and cell signaling were overrepresented amongst the differentially expressed genes.
  • Seventeen enriched pathways were identified, which could be categorized as being involved in the extracellular matrix turnover, protein metabolism, and growth factor signaling.
  • Furthermore, network analysis revealed clusters of differentially expressed genes involved in extracellular matrix organization, endothelial regulation, and cellular metabolism.

Conclusions

  • Overrepresented GO terms and enriched pathways suggest a condition of high metabolic activity and tissue turnover in the osteoarthritis-affected tissue. This could mean that the synovium may still have the capacity to heal itself and maintain homeostasis in the early stages of the disease.
  • The identified differentially expressed genes within key pathways show potential as diagnostic markers or therapeutic targets for PTOA.
  • The study’s limitations include a small sample size and the capture of a single point post-injury. Therefore, mechanistic validation of these findings is proposed as the next step in this study.

Cite This Article

APA
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN. (2020). Differential gene expression analysis reveals pathways important in early post-traumatic osteoarthritis in an equine model. BMC Genomics, 21(1), 843. https://doi.org/10.1186/s12864-020-07228-z

Publication

BMC genomics
ISSN: 1471-2164
NlmUniqueID: 100965258
Country: England
Language: English
Volume: 21
Issue: 1
Pages: 843
PII: 843

Researcher Affiliations

McCoy, Annette M
  • Department of Veterinary Clinical Medicine, University of Illinois Urbana-Champaign, 1008 W Hazelwood Dr, Urbana, IL, USA. mccoya@illinois.edu.
Kemper, Ann M
  • Department of Veterinary Clinical Medicine, University of Illinois Urbana-Champaign, 1008 W Hazelwood Dr, Urbana, IL, USA.
Boyce, Mary K
  • Veterinary Population Medicine Department, University of Minnesota, 1365 Gortner Ave, St. Paul, MN, USA.
  • Present Address: Crossroads Veterinary Clinic, Anderson, CA, USA.
Brown, Murray P
  • Department of Large Animal Clinical Sciences, University of Florida, 2015 SW 16th Avenue, Gainesville, FL, USA.
Trumble, Troy N
  • Veterinary Population Medicine Department, University of Minnesota, 1365 Gortner Ave, St. Paul, MN, USA.

MeSH Terms

  • Animals
  • Gene Expression
  • Gene Expression Profiling
  • Gene Ontology
  • Horses
  • Osteoarthritis / genetics
  • Synovial Membrane

Grant Funding

  • ILLU-888-387 / National Institute of Food and Agriculture

Conflict of Interest Statement

The authors declare that they have no competing interests.

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